Homoharringtonine Combined with Cytarabine to Treat Chronic Myelogenous Leukemia in Myeloid Blast Crisis and Its Impact on Bone Marrow CD34+CD7+ Cells

Li, Yuanyuan; Deng, Zhong‐Liang; Zho, Jiabin; Ding, Banhe; Shi, Yuye; Li, Yufeng

doi:10.1159/000356742

Cited by 4 publications

(4 citation statements)

References 17 publications

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“…296 The study concluded that it is an effective treatment and that CD34 þ CD7 þ cells may be one of the valuable clinical parameters to assess treatment effectiveness.…”

Section: Other Clinical Applicationsmentioning

confidence: 99%

Cephalotaxus Alkaloids

Pérard-Viret

Quteishat

Alsalim

et al. 2017

The Alkaloids: Chemistry and Biology

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Cephalotaxus alkaloids represent a family of plant secondary metabolites known for 60 years. Significant activity against leukemia in mice was demonstrated for extracts of Cephalotaxus. Cephalotaxine (CET) (1), the major alkaloid of this series was isolated from Cephalotaxus drupacea species by Paudler in 1963. The subsequent discovery of promising antitumor activity among new Cephalotaxus derivatives reported by Chinese, Japanese, and American teams triggered extensive structure elucidation and biological studies in this family. The structural feature of this cephalotaxane family relies mainly on its tetracyclic alkaloid backbone, which comprises an azaspiranic 1-azaspiro[4.4]nonane unit (rings C and D) and a benzazepine ring system (rings A and B), which is linked by its C3 alcohol function to a chiral oxygenated side chain by a carboxylic function alpha to a tetrasubstituted carbon center. The botanical distribution of these alkaloids is limited to the Cephalotaxus genus (Cephalotaxaceae). The scope of biological activities of the Cephalotaxus alkaloids is mainly centered on the antileukemic activity of homoharringtonine (HHT) (2), which in particular demonstrated marked benefits in the treatment of orphan myeloid leukemia and was approved as soon as 2009 by European Medicine Agency and by US Food and Drug Administration in 2012. Its exact mechanism of action was partly elucidated and it was early recognized that HHT (2) inhibited protein synthesis at the level of the ribosome machinery. Interestingly, after a latency period of two decades, the topic of Cephalotaxus alkaloids reemerged as a prolific source of new natural structures. To date, more than 70 compounds have been identified and characterized. Synthetic studies also regained attention during the past two decades, and numerous methodologies were developed to access the first semisynthetic HHT (2) of high purity suitable for clinical studies, and then high grade enantiomerically pure CET (1), HHT (2), and analogs.

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“…296 The study concluded that it is an effective treatment and that CD34 þ CD7 þ cells may be one of the valuable clinical parameters to assess treatment effectiveness.…”

Section: Other Clinical Applicationsmentioning

confidence: 99%

Cephalotaxus Alkaloids

Pérard-Viret

Quteishat

Alsalim

et al. 2017

The Alkaloids: Chemistry and Biology

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“…HHT (Synribo) is thought to act as a broad-spectrum protein tyrosine kinase inhibitor and was approved in 2012 by the FDA for the treatment of adult patients with CML or accelerated phase CML [ 49 ]. The therapeutic response of patients with CML in myeloid blast crisis (CML-MBC) is generally very poor, but a combination of HHT and cytarabine has been reported to be an effective treatment for CML-MBC [ 50 ].…”

Section: Cancer Chemotherapeutic Agents Derived From Terrestrial Planmentioning

confidence: 99%

Natural Products as a Vital Source for the Discovery of Cancer Chemotherapeutic and Chemopreventive Agents

Cragg¹,

2015

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Throughout history, natural products have played a dominant role in the treatment of human ailments. For example, the legendary discovery of penicillin transformed global existence. Presently, natural products comprise a large portion of current-day pharmaceutical agents, most notably in the area of cancer therapy. Examples include Taxol, vinblastine, and camptothecin. These structurally unique agents function by novel mechanisms of action; isolation from natural sources is the only plausible method that could have led to their discovery. In addition to terrestrial plants as sources for starting materials, the marine environment (e.g., ecteinascidin 743, halichondrin B, and dolastatins), microbes (e.g., bleomycin, doxorubicin, and staurosporin), and slime molds (e.g., epothilone B) have yielded remarkable cancer chemotherapeutic agents. Irrespective of these advances, cancer remains a leading cause of death worldwide. Undoubtedly, the prevention of human cancer is highly preferable to treatment. Cancer chemoprevention, the use of vaccines or pharmaceutical agents to inhibit, retard, or reverse the process of carcinogenesis, is another important approach for easing this formidable public health burden. Similar to cancer chemotherapeutic agents, natural products play an important role in this field. There are many examples, including dietary phytochemicals such as sulforaphane and phenethyl isothiocyanate (cruciferous vegetables) and resveratrol (grapes and grape products). Overall, natural product research is a powerful approach for discovering biologically active compounds with unique structures and mechanisms of action. Given the unfathomable diversity of nature, it is reasonable to suggest that chemical leads can be generated that are capable of interacting with most or possibly all therapeutic targets.

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“…In a small study of 34 patients treated with HA regimen, the overall HR rate was 60% and 21% had a cytogenetic response. 54 …”

Section: Homoharringtonine-based Regimensmentioning

confidence: 99%

“…In a small study of 34 patients treated with HA regimen, the overall HR rate was 60% and 21% had a cytogenetic response. 54 HHT-based therapies appear promising and merit further investigation in combination with third-generation TKIs.…”

Section: Homoharringtonine-based Regimensmentioning

confidence: 99%

Current Management of Chronic Myeloid Leukemia Myeloid Blast Phase

Yohannan

George

2022

Clin Med Insights Oncol

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Despite the major advancements in the management of chronic phase (CP) chronic myeloid leukemia (CML), blast crisis (BC) remains a major therapeutic challenge. BC can be myeloid, lymphoid, or mixed lineage with myeloid BC being the most common type. BC in CML is mediated by aberrant tyrosine kinase activity of the BCR::ABL fusion protein. The introduction of BCR::ABL tyrosine kinase inhibitor (TKI) has been a gamechanger in the treatment of CML and there has been a significant reduction in the incidence of BC. The main treatment goal in BC is to achieve a second CP and consolidate that with an allogeneic stem cell transplantation (SCT) in eligible patients. The outcomes in BC remain dismal even in the current era. In this review, we provide an overview of the biology and current therapeutic approach in myeloid BC.

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Homoharringtonine Combined with Cytarabine to Treat Chronic Myelogenous Leukemia in Myeloid Blast Crisis and Its Impact on Bone Marrow CD34+CD7+ Cells

Cited by 4 publications

References 17 publications

Cephalotaxus Alkaloids

Cephalotaxus Alkaloids

Natural Products as a Vital Source for the Discovery of Cancer Chemotherapeutic and Chemopreventive Agents

Current Management of Chronic Myeloid Leukemia Myeloid Blast Phase

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